ArticleAmerican journal of cancer research2019
PDE3A inhibitor anagrelide activates death signaling pathway genes and synergizes with cell death-inducing cytokines to selectively inhibit cancer cell growth.
Article in American journal of cancer research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 28 citations in OpenAlex.
- Repurposed cAMP-Modulating Agents Enhance 5-Fluorouracil Response Through Membrane-Dependent Mechanisms.Membranes · 2026Review
- Preclinical response of uveal melanomas to the velcrin compound, BAY 2666605.Molecular cancer therapeutics · 2026Article
- Pan-cancer ex vivo target evaluation of phosphodiesterase 3 A (PDE3A).Journal of molecular medicine (Berlin, Germany) · 2026Article
- The Role of PDE3A in Cancer.ACS omega · 2026Review
- Clinical and Functional Characterization of PDE1A as a Wnt/Oncology research · 2026Article
- Pharmacokinetic profile andDrug delivery · 2025Article
- Phosphodiesterase 3 A expression in gastrointestinal stromal tumors.Virchows Archiv : an international journal of pathology · 2025Article
- Anagrelide and idarubicin combination induces GSDME-mediated pyroptosis as a potential therapy for high-PDE3A acute myeloid leukemia.Leukemia · 2025Article
- First-in-Human Dose-Escalation Study of the First-in-Class PDE3A-SLFN12 Complex Inducer BAY 2666605 in Patients with Advanced Solid Tumors Coexpressing SLFN12 and PDE3A.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- A PDE3A-SLFN12 Molecular Glue Exhibits Significant Antitumor Activity in TKI-Resistant Gastrointestinal Stromal Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Initial Low-Dose Hydroxyurea and Anagrelide Combination in Essential Thrombocythemia: Comparable Response with Lower Toxicity.Journal of clinical medicine · 2024Article
- Article
- Anagrelide: A Clinically Effective cAMP Phosphodiesterase 3A Inhibitor with Molecular Glue Properties.ACS medicinal chemistry letters · 2023Article
- ETV1 inhibition depressed M2 polarization of tumor-associated macrophage and cell process in gastrointestinal stromal tumor via down-regulating PDE3A.Journal of clinical biochemistry and nutrition · 2023Article
- Velcrin-induced selective cleavage of tRNANature chemical biology · 2023Article
- Structural, molecular, and functional insights into Schlafen proteins.Experimental & molecular medicine · 2022Review
- Transcriptome Profiling of A549 Xenografts of Nonsmall-cell Lung Cancer Treated with Qing-Re-Huo-Xue Formula.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Structure of PDE3A-SLFN12 complex and structure-based design for a potent apoptosis inducer of tumor cells.Nature communications · 2021Article
- Structure of PDE3A-SLFN12 complex reveals requirements for activation of SLFN12 RNase.Nature communications · 2021Article
- Identifying Susceptibility Loci for Cutaneous Squamous Cell Carcinoma Using a Fast Sequence Kernel Association Test.Frontiers in genetics · 2021Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We performed a drug repurposing screening of a US Food and Drug Administration (FDA)-approved drug compound library and identified Anagrelide (ANA), a known phosphodiesterase 3A (PDE3A) inhibitor, that selectively and potently inhibited the growth of cancer cells. However, inactivation of PDE3A or knocking-down its gene expression did not inhibit cancer cell growth. It was the interaction of ANA with PDE3A that created a new function of PDE3A to alter the activities of another unknown function protein SLFN12 to cause the inhibition of cancer cell growth. The expressions of both PDE3A and SLFN12 were required for ANA to inhibit cancer cell growth. Depletion of PDE3A or SLFN12 led to ANA resistance. Furthermore, the effects of ANA on different cancer cells were different depending on the expression levels of PDE3A and SLFN12, causing G0/G1 cell cycle arrest in the cells expressing lower levels of SLFN12, but apoptosis in the cells expressing higher levels of the two proteins. Further investigation into the molecular mechanisms of the ANA-induced cell cycle arrest and apoptosis identified a set of cell cycle and apoptosis-related genes whose expressions were altered by ANA treatment. ANA also synergized with the cell death-inducing cytokines IFN-α, IFN-γ, TNF-α, or TRAIL, which regulated the same set of genes as ANA did, to induce apoptosis of the cancer cells. Our study uncovered new activities, functions, and mechanisms of ANA and SLFN12 and provided a diagnosis method to precisely use ANA as an anti-cancer drug. It also revealed PDE3A and SLFN12 as new anti-cancer drug targets for developing novel anti-cancer therapies.
Indexed as
Identifiers
31598394PMC6780660W2990757573What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.